Description

Nelio tablets contain the drug benazapril, which has an effect on the kidneys and blood circulation. Nelio is helpful for dogs with heart failure and for cats with reduced kidney function. Both cats and dogs will often eat Nelio flavoured tablets spontaneously, but they can be given in food if it is easier. They are recommended to be given just once daily

Clinical particulars

Target species

Indications for use

Contra-indications

Do not use in case of known hypersensitivity to ACE inhibitors or to any ingredient of the product.

Special warnings for each target species

None

Special precautions for use

Efficacy and safety of benazepril have not been established in cats of weight less than 2.5 kg

No evidence of renal toxicity to benazepril has been observed in cats during clinical trials.

However, as is routine in cases of renal insufficiency, it is recommended to monitor plasma urea and creatinine levels.

Adverse reactions

Benazepril may cause mild, intermittent diarrhea in a small proportion of cats.

In cats with chronic renal insufficiency, benazepril may increase plasma creatinine concentrations at the start of therapy. This effect is related to the therapeutic effect of the product in reducing blood pressure, and therefore is not necessarily a reason to stop therapy in the absence of other signs.

Benazepril reduced erythrocyte counts in normal cats at high doses, but this effect was not observed at the recommended dose during clinical trials in cats with chronic renal insufficiency. As is routine in cases of chronic renal insufficiency, it is recommended to monitor erythrocyte counts during therapy.

Emesis, anorexia, dehydration and lethargy have been reported in rare occasions in cats.

Use during pregnancy or lactation

Laboratory studies in rats have shown embryotoxic effects of Benazepril at non-maternotoxic doses (urinary system abnormalities in foetus). Benazepril administered to cats at a daily dose of 10 mg / kg for 52 weeks resulted in the reduction of ovary / oviduct weights. Safety of this product has not been tested in pregnant or lactating queens.

Do not use in pregnant or lactating females or in queens intended for breeding.

Interactions

Blood pressure may be monitored during anesthesia in cats receiving benazepril.

Interactions with potassium preserving diuretics like spironolactone, triamterene or amiloride cannot be ruled out. It is recommended to monitor plasma potassium levels when using benazepril in combination with a potassium sparing diuretic as life threatening reactions are a possibility.

Amounts to be administered and administration route

Oral administration of 0.46 mg of benazepril per kg and per day, equivalent to 0.50 mg of benazepril hydrochloride per kg and per day, as one administration, whether or not with a meal, i.e one Nelio 2.5 mg tablet per 5 kg body weight or one Nelio 5 mg tablet per 10 kg body weight.

In case of use of half tablets: Put the remaining half of the tablet back into the blister pocket and use for the next administration.

The tablets are flavoured and may be taken spontaneously by cats, but can also be administered directly into the cat's mouth or be given with food if necessary.

Overdose

Transient and reversible signs of hypotension may appear in case of accidental overdose. Treatment is symptomatic, involving intravenous infusion with warm isotonic saline.

In cats a 10-fold overdosage daily for one year was asymptomatic.

Withdrawal periods

Not Applicable

Pharmacological particulars

Pharmacodynamic properties

Benazepril hydrochloride is a prodrug hydrolysed in vivo to benazeprilat. This active metabolite inhibits angiotensin converting enzyme (ACE), thus preventing the conversion of inactive angiotensin I into active angiotensin II. Therefore, benazeprilat inhibits all effects induced by angiotensin II, in particular, vasoconstriction of both arteries and veins and retention of sodium and water by the kidney. Benazeprilat causes long-lasting inhibition of plasma ACE, with significant inhibition persisting for 24 hours after a single dose.

In cats with renal insufficiency, benazepril reduces systemic and intraglomerular blood pressure. At the same time, it decreases glomerular basal membrane permeability. In consequence, it reduces protein loss in the urine and renal insufficiency progression.

Pharmacokinetic properties

After oral administration, benazepril is rapidly absorbed from the gastrointestinal tract. One part of absorbed benazepril is hydrolyzed by hepatic enzymes to the active substance, benazeprilat; unchanged benazepril and hydrophilic metabolites account for the remainder. The absolute systemic bioavailability, calculated for oral benazepril versus intravenous benazepril is about 9% both in fasting and fed situations. After administration of Nelio 5 at 0.65 mg/kg in cats, peak benazeprilat concentrations (approximately 110 ng/ml) are achieved within about 1 and half hours. The apparent terminal half-life of benazeprilate was 12.5 h

Benazepril and benazeprilat are both extensively bound to plasma proteins.

Repeated administration leads to slight accumulation of benazeprilat in plasma, steady state being achieved in less than 4 days.

In cats, benazeprilat is excreted 85% via the biliary route and 15% via the urinary route. The clearance of benazeprilat is not affected in cats with decreased glomerular filtration; therefore no adjustment of the dose is required.

Disposal

Any unused veterinary medicinal product or waste materials derived from such veterinary medicinal products should be disposed of in accordance with local requirements.

Marketing Authorisation Holder (if different from distributor)

Sogeval SA

Marketing authorisation number

Nelio 2.5 mg Tablets for Cats: Vm 20749/4018.

Nelio 5 mg Tablets for Cats: Vm 20749/4012

Date of the first authorisation or date of renewal

Nelio 2.5 mg Tablets for Cats: 16 February 2010

Nelio 5 mg Tablets for Cats: 27 February 2009

Date of revision of the text

Nelio 2.5 mg Tablets for Cats: February 2010

Nelio 5 mg Tablets for Cats: February 2009

Any other information

Special precautions to be taken by the person administering the veterinary medicinal product to animals: Pregnant women should take special care to avoid accidental oral exposure, because ACE inhibitors have been found to affect the unborn child during pregnancy in humans.

Wash hands after use. In case of accidental ingestion by children, seek medical advice immediately and show this label to the doctor.

Indications for use

Contra-indications

Do not use in case of known hypersensitivity to ACE inhibitors or to any ingredient of the product.

Do not use in any dog that has evidence of cardiac output failure, for example, due to aortic stenosis

Special warnings for each target species

None

Special precautions for use

No evidence of renal toxicity to benazepril has been observed during clinical trials.

However, as is routine in cases of renal insufficiency, it is recommended to monitor plasma urea and creatinine levels.

Adverse reactions

At the start of the treatment, a decrease of the blood pressure and a transient increase of plasmatic concentrations of creatinine may occur.

On rare occasions, transient signs of hypotension, such as lethargy and ataxia may occur.

Use during pregnancy or lactation

Studies in laboratory animals (rats) have shown embryotoxic effects (malformations of the fœtal urinary system) at doses not toxic for the mother. The safety of the medicinal product has not been studied in pregnant or lactating females.

Do not use during pregnancy or lactation. Do not use in breeders.

Interactions

None known in dogs. In dogs with heart failure, benazepril has been given in combination with digoxin, diuretics and anti-arrhythmic drugs without demonstrable adverse interactions.

Interactions with potassium sparing diuretics, like spironolactone, triamteren and amiloride, can not be excluded.

The concurrent administration of potassium-sparing diuretics should only be considered under regular monitoring of plasma potassium.

The association of this product with other anti-hypertensive agents (e.g.: calcium channel blockers, β-blockers or diuretics), anaesthetics or sedatives may lead to additive hypotensive effect.

In humans, the association of ACE inhibitors and NSAIDs can lead to reduced anti-hypertensive efficacy or impaired renal function. Therefore concurrent administration with NSAIDs or other medications with hypotensive effect should be considered with care.

The concomitant administration of NSAIDs or ciclosporin requires a survey of the renal function.

Amounts to be administered and administration route

Oral administration 0.23 mg of benazepril per kg bodyweight per day, equivalent to 0.25 mg of benazepril hydrochloride per kg bodyweight per day, as one administration, with or without a meal, i.e one Nelio 5 mg tablet per 20 kg body weight and one Nelio 20 mg tablet per 80 kg body weight.

In case of use of quarters or half tablets: Put the remaining quantity of the tablet back into the blister pocket and use for the next administration.

The dose may be doubled, still administered once daily, if judged clinically necessary and advised by the veterinary surgeon.

The tablets are flavoured and may be taken spontaneously by dogs, but can also be administered directly into the dog’s mouth or be given with food if necessary.

Overdose

Transient and reversible signs of hypotension may appear in case of accidental overdose. Treatment is symptomatic, involving intravenous infusion with warm isotonic saline.

Morphologic changes such as hypertrophy or hyperplasia of juxtaglomerular cells, increase of uremia and a weight loss of the heart due to an involution have been observed with doses over 10 mg/kg in healthy dogs.

Withdrawal periods

Not Applicable

Pharmacological particulars

Pharmacodynamic properties

Benazepril hydrochloride is a prodrug hydrolysed in vivo to benazeprilat which inhibits angiotensin converting enzyme (ACE), thus preventing the conversion of inactive angiotensin I into active angiotensin II. Therefore, benazeprilat inhibits all effects mediated by angiotensin II, including vasoconstriction of both arteries and veins and retention of sodium and water by the kidney. Benazeprilat causes long-lasting inhibition of plasma ACE, with significant inhibition persisting for 24 hours after a single dose.

In dogs with heart failure, benazepril reduces the peripheral resistance, blood pressure of left ventricle and volume load on the heart.

Pharmacokinetic properties

Following oral administration, benazepril is rapidly absorbed from the gastrointestinal tract. Absorbed benazepril is partly hydrolyzed by hepatic enzymes to the active substance, benazeprilat; unchanged benazepril and hydrophilic metabolites account for the remainder. The absolute systemic bioavailability, calculated for oral benazepril versus intravenous benazepril is about 5-8 %, because of incomplete absorption and first pass metabolism.. After oral administration of 0.5 mg/kg of benazepril hydrochloride, peak benazeprilat plasmatic concentrations (Cmax approximately 30 ng.ml-1) are achieved within about 1 and half hours. The plasmatic concentrations (AUCtot) area under the curve is close to 193 ng.h.mL-1

Benazepril and benazeprilat are both extensively bound to plasma proteins and in tissue it mainly resides in kidney and liver. There is no significant difference in the pharmacokinetics, whether benazepril hydrochloride is administered to fed or fasted dogs.

The elimination half-life of benazeprilate is approximately 13 hours.

Repeated administration leads to slight accumulation, steady state being achieved in less than 4 days.

In dogs, benazepril is equally excreted by hepatic or urinary route.

The clearance of benazepril is not appreciably affected in dogs with impaired renal or hepatic functions and therefore no adjustment of the dose is required in cases of renal insufficiency.

Disposal

Any unused veterinary medicinal product or waste materials derived from such veterinary medicinal products should be disposed of in accordance with local requirements.

Marketing Authorisation Holder (if different from distributor)

Sogeval SA

Marketing authorisation number

Nelio 5 mg Tablets for Dogs: Vm 20749/4015.

Nelio 20 mg Tablets for Dogs: Vm 20749/4016.

Date of the first authorisation or date of renewal

Nelio 5 mg and 20 mg tablets for Dogs: 7 September 2009

Date of revision of the text

Nelio 5 mg and 20 mg tablets for Dogs: September 2009

Any other information

Special precautions to be taken by the person administering the veterinary medicinal product to animals: Pregnant women should take special care to avoid accidental oral exposure, because ACE inhibitors have been found to affect the unborn child during pregnancy in humans.

Wash hands after use. In case of accidental ingestion by children, seek medical advice immediately and show this label or the package leaflet to the doctor.

Legal category

POM-V

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